Table of Content

24 February 2005, Volume 26 Issue 1

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The effects of Research Innovation on Pharmaceutical Education

Wang Xiulan;Peng Shiqi

2005, 26(1):  1-3. 

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Based on the recognition and comprehension of the current situation of pharmaceu tical colleges and departments in our country in the present paper the contribut ions of educational, scholastic and research innovation in the development of th ecolleges and departments were discussed. In our opinion research innovation may enhance educational innovation and scholastic innovation and is a basic one. Consequently research innovation is taken as the essential element for the development of our college may be reasonable.

Advance of Disease Control Strategy and Preventive Pharmaceutics

Yang Xiaoda;Wang Kui

2005, 26(1):  3-6. 

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On the basis of the development of modern biology, especially complex system biology and molecular medicine, it is anticipated that the future trend of medicine is towards its predictiveness, preventiveness and individuality. The change of human illness spectrum makes the demand on illness prevention a more serious one. All these changes and development call on a comprehensive hygiene-promoting system as well as the further development of preventive pharmaceutical science. It studies the key aspects of illness from its onset to its further development o n cellular level, to discover risk factors of diseases and their biological mark ers, as well as to establish indicative and predicative measures, the preventive pharmaceutical science explores further on the basis of the aforementioned the mechanism of the intervening of illness, the screening, design and discovery of preventive drugs which are pertinent to the individual illness. China has some a dvantages in several respects of preventive medicine development. The preventive pharmaceutical science will bring about innovations and advances in multiple le vels and aspects of the society, such as pharmaceutical industry, drug and food administration as well as the fundamental scientific research.

A Brief Overview of the Pharmacy Education in Canada

Cui Guohui;Wang Lili

2005, 26(1):  7-8. 

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Delivery Systems in Gene Therapy

Liu Hu;Anas El-Aneed;Cui Guohui

2005, 26(1):  9-20. 

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Hybrid Materials of Polymer Gels with Surfactants

Hu Yan;Kaoru Tsujii

2005, 26(1):  21-32. 

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Advance of Pseudopeptide TreatingThrombosis and Osteoporosis

Wei Xin;Wang Weiwei;Cui Guohui;Zhao Ming;Wang Chao;Peng Shiqi

2005, 26(1):  33-36. 

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In the present paper the design of oligopeptides and pseudopeptides treating thr ombosis and osteoporosis, such as peptide 6A and its analogs, hybrid peptides of peptide 6A or its analogs and RGD peptides, cyclic peptide 6A or its analogs, nitronyl nitroxide containing peptide 6A or its analogs and RGD peptides, estrogen-GHRPs, hydrocortisone-Kyotophin, hydrocortisone-urotoxins, prednisolone-urotoxins, and estrogen-RGD peptides, was reviewed.

Effects of Icarrin and Its Metabolites on the Bone Metabolism in vitro

Zhang Tianlan;Huang Jian;Xu Shanjin;Wang Kui

2005, 26(1):  37-37. 

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The major and active constituents of the genus Epimedium are flavonoids, which can prevent bon e loss in ovariectonized rats. Icarrin is a flavonoid isolated from Herba Epimed ii. By enzymatic and acidic hydrolysis of icarrin, two metabolites (icariside Ⅱ and icaritin) can be obtained. Here we report the effects of icarrin and its tw o metabolites on the bone formation and bone resorption in vitro.Three cell models were used. Primary osteoblastic cells were isolated from neona tal Wistar rat calvarias. Icarrin and its two metabolites increased the viabilit y of osteoblasts significantly. Besides, alkaline phosphatase (ALP) activity and osteocalcin (OC) synthesis of osteoblasts also increased, as well as the ALP, O C and collagen mRNA expression. Since ALP and OC are phenotypic markers for earl y-stage differentiated osteoblasts and terminally differentiated osteoblasts re spectively, our findings indicate that Icarrin and its metabolites stimulate ost eoblasts differentiation at various stages (from osteoprogenitors to terminally differentiated osteoblasts). The effects of Icarrin and its metabolites on osteoclast-like cells were obtain ed by coculturing bone marrow with osteoblasts for 8 days in α-MEM containing 10^-8mol/L 1.25(OH)₂D₃. The osteoclast-like cell formation was estimat ed by staining for tartrate-resistant acid phosphatase (TRACP), a marker enzyme of osteoclast. Icarrin and its metabolites significantly inhibited osteoclast-like cell formation, and elevated the mRNA levels of OPG and RANKL dose-depend e ntly, resulting in enlarged ratio of the two as revealed by RT-PCR. Hence it is likely that icarrin and its metabolites regulate bone resorption, at least in part, via its effects on OPG and RANKL expression.Mature osteoclasts were isolated from the long bones of neonatal Japanese white rabbits (60-90g). The surface area of bone resorption lacunae was measured by p hotomicrography and image analysis. Actin microfilaments were detected by bindin g of rhodamine-conjugated phalloidin (R-PHD) to F-actin. Icarrin and its meta bolites showed the potency to withdraw the actin ring, consistent with the inhib ited bone resorption of osteoclasts. In conclusion, icarrin and its metabolites can not only interfere with the diffe rentiation of osteoclast-like cells and inhibit bone resorption ability of matu re osteoclasts, but also promote bone formation.

Modification of 3S-1,2,3,4-Tetrahydro-β-carboline-3-carboxylic Acid and Anti-thrombosis Activities

Xue Baoyu;Jiang Weixin;Yang Zhe;Zhao Ming;Peng Shiqi;Wang Weiwei 

2005, 26(1):  38-38. 

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3S-1,2,3,4-Tetrahydro-β-carboline-3-carboxylic acid (1) is a substance from an edible vegetable in China, and antiaggregation active. In the corresponding investigation we found that in both organic solvent and water 1 was purely soluble and had low bioavailability. It was also well kown that in some cases the bioavailability of some water insoluble compou nds may be enhanced by amino acid modification. In the present paper the L-amino acids were introduced into 3-position of 1 and the anti-thrombosis activ ities were assayed in vitro and in vivo. In the presence of H₂SO₂ the Pictet-Spengler condensation of L-tryptophane and formaldehyde provided 1 in 95% yield. The ami dation of 1 and Boc 2O offered 3S-N-Boc-1,2,3,4-tetrahydr o-β-carboline-3-carboxylic acid (2) in 76% yield. Couplling 2 and L-amino acid methyl esters 3S-N-Boc-1,2,3, 4-tetrahydro-β-carboline-3-carboxyl-L-amino acid esters 3 a-n were obtained in 90%-98% yields. The saponification of 3 a-n in aqueous sodium hydroxi de provided 3S-N-Boc-1,2,3,4-tetrahydro-β-carboline-3-carboxyl-L-amino acids 4 a-n in 90%-98% yields. In the solution of hydrigen chloride/ethyl acetate the Boc group 4 a-n was removed and 5 a-n were obtained in 80%-95% yields. The in vitro and in vivo assays indicated that introducing amino acids resulted in different change in the anti-thrombotic activity of 1. Fo r instance introducing amino acid with acidic or rigidly cyclic side chain did n ot enhance the anti-thrombotic activity of 1, introducing ami no acid with hydrophorbic side chain moduratly enhance the anti-thrombotic acti vity of 1, and introducing amino acid with heteroatomic or basic side chain significantly enhance the anti-thromboti c activity of 1. The apparent permeability coefficient experim ents demonstrated that introducing the amino acid with acidic or rigidly cyclic side chain does not increase the a pparent permeability coefficient of 1, introducing the amino acid with hydrophorbic side chain moduratly increases the a pparen t permeability coefficient of 1, and introducing the amino acid with heteroatomic or basic side chain significantly increase enhance the the a p parent permeability coefficient.

Nitormethylation and Nitroethylation of 3,17-Dioxo-steroids

Xue Baoyu;Jiang Weixin;Wu Guofeng;Peng Shiqi;Zhao Ming

2005, 26(1):  39-39. 

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Some investigations discovered that estradiol has specific affinity to the tumor sites. With estradiol as the carrier chlorambucil can accumulate specifically t o the tumor sites and exhibit a strong antitumor effect. Among the reported estr adiol carriers 1-methyl-3-hydroxy-1,3,5(10),9(11)-estratetraene-17-one (1) is characterized by high affinity to the tumor sites and low estrogenic activity, and thus exhibits promising use. In the present pa per nitormethylation and nitroethylation of 11-α-hydroxyandrosta-1,4-diene-3,17-dione (2) and 1,4,9(11)-androstatriene-3,17-d ione (3) were investigated. With ethylenediamine as the catalyst refluxing 2 and nitromethane the condensation s electively occurred at the 17-carbonyl and gave 11α-hydroxy-17-nitromethyl-ideneandrosta-1,4-diene-3-one in 60% yield no any reaction occurred at 3-carbonyl. With the same procedure the condensation of 2 and nitroethane exclus ively gave 11α,17β-dihydroxy-17α-ethylandrosta-1,4,8(14)-triene-3-one in 23% yield neither 17-nor 3-carbonyl nitroethylation product was obtained. In the presence of tosyl chloride and pyridine 2 was co nverted into 11α-p-to luenesulfonyloxyandrosta-1,4-diene-3,17-dione (4) in 94% yield. At 90 ℃ in the presence of potassium acetate and acetic anhydrid e 4 was eliminated and 3 was obt ained in 80% yield. Refluxing the mixture of nitromethane and 3 for 1 h, removing at least 10% of nitromethane via distillatio n, treating the residue with ethylenediamine, and refluxing the mixture for anot her 1 h gave specifically 1 in 96% yield. Refluxing the mixture of 3, notromethane and ethylenediamine the cond ensation gave 17-nitrome thylidene-1,3,11(12)-androstatriene-3-one (5) in 45% yield. Under the same conditions and increasing the amount of ethylenediamine t he simultaneously nitromethylation of 3-and 17-carbonyl of 3 resulted in 1 and 5 in 50% and 40% yield, respectively. Refluxing the mixture of 3, notroethane and ethylenediamine the condensation gave 17β-hydroxy-17α-ethyl-androsta-1,4,8(14),9(11)-tetraene-3-one in 17% yield.

The Study of Mitochondrial Status and Calcium Homeostasis in Aged Brain Slices of Mice

Xiong Jie

2005, 26(1):  40-40. 

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Change in “calcium homeostasis” is one of the mechanisms that proposed to expl ain the age-dependent injuries of neurons. But what is the most reliable age-a ssociated changes in neuronal Ca²⁺ homeostasis, and are these changes prim ary or secondary to other changes in the physiology of the aged neurons? Here we used the most physiological in vitro preparation-the parasagittal cerebellar slices, obtained from animals of different ages (11-23 months)-to perform sim ultaneous measurements of both intracellular calcium ([Ca²⁺]_i) and mit ochondrial membrane potential (MMP) in real time. A 15-second pulse of glutamat e, kainic acid (KA) or N-methyl-D-aspartic acid (NMDA) was used to trigger a calcium signal. No changes were found on the mean resting [Ca²⁺]_i values of aged neurons, while the MMP already sho wed a significant decrease. Most of the changes in the calcium homeostasis appea red only when the aged neurons were exposed to higher levels of stimulation and the most significant change was the decreased recovery rate of calcium signal, t ogether with a delayed recovery of MMP. The close and significant (P< 0.00 1) correlation between the status of neuronal mitochondria and [Ca²⁺]_i 1 minute after the remove of stimulation indicated that the changes of calcium ho meostasis were secondary to the impairment of mitochondrial function.

Synthesis and NO Scavenging Activity of 2-Substitutea nitronyl Nitroxides

Zhang Guijuan;Jiang Weixin;Li Zheng;Zhao Ming;Peng Shiqi;Wang Chao

2005, 26(1):  41-41. 

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The ability scavenging nitric oxide makes nitronyl nitroxides to be promising dr ugs for the treatments of various diseases caused by excess production of NO. Id entifying the preferential structure for the NO scavenger in the present paper the 2-alkyl, 2-heterocycle and 2-substitutedphenylnitronyl nitroxides were syn thesized and their in vitro NO scavenging activities were assayed. In the presen ce of Br 2 and NaOH 2-nitropropane was smoothly converted into di-tert-butyl bishydroxylamine (1) in 40% total yield. The condensatio n of 1 and corresponding a ldehydes provided the corresponding 2-substituted-1,3-dihydroxy-4,4,5,5-tet ramethylimidazolindine 2a-h in 5 3%, 69%, 83%, 73%, 69%, 85%, 51%, and 63% yield, respectively. With PbO 2 as oxidation agent 2a-h were converted into the cor responding nitronyl nitroxides 3a-h in 99%, 38%, 88%, 83%, 79%, 80%, 52% and 7 3% yield, respectively. In the ESR measurements 3a-h gave typical NO spectra, d emonstrating they were chemically stable free radicals. In the aortic strip expe riments 3a-h dose-dependently an d 2-substituent-dependently inhibited Ach-i nduced vasorelaxation. 100 μmol/L and 10 μmol/L of 3a-h exhibited obvious NO scavenging activity(compare to vehicle, P<0.001). At the concentration of 1 μmol/L however only 4-hydroxyphenylnitronyl nitroxide (3g) exhibited obvious NO scavenging effect (compare to ve hicle, P<0.001). The activities of the hig h dose were higher than that of moderate dose (P<0.001) and the activities o f the moderate dose were higher than that of low dose (P< 0.001). Based on the observations it is concluded that nitronyl nitroxides are useful NO scavenger and 2-substitutednitronyl nitroxide may be selected as the desirable lead compo und in the development of NO scavenger.Based on the observations that 2-substit utedphenylnitronyl nitroxides were chemically most stable and bioactive it is co ncluded that nitronyl nitroxides are useful NO scavenger and 2-substitutedpheny lnitronyl nitroxide may be selected as the desirable lead compound in the development of NO scavenger.

Synthesis, Free Radical Scavenging and Thrombolytic Activities of Nitronyl Nitroxide Modified Peptide 6A and Analogues

Zhang Guijuan;Jiang Weixin;Liu Junling;Zhao Ming;Peng Shiqi;Zhang Jianwei

2005, 26(1):  42-42. 

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Nitric oxide is involved in ischemia/reperfusion brain injury. Ischemic brain in jury and ischemia/reperfusion brain injury always associate with thrombogenesis and thrombolysis. Considering the specific ability scavenging free radicals of n itronyl nitroxides and the thrombolytic activity of the oligopeptides (ARPAK, GR PAK and QRPAK), [1-(1',3'-dioxyl-4',4',5',5'-tetra-methyldihydroimidazol-2-yl)phenyl-4-yl]oxyacetic acid (1) was introduced into their N-terminal via six reactions in 27% tota l yield. The ESR measurement demonstrates that the conjugates N-[1-(1',3'-dioxyl-4',4',5',5'-tetramethyldihydroimidazol-2-yl)-phenyl-4-yl]oxya cetyl-ARPAK (2a),-GRPAK (2b) and-QRPAK (2c) are stable NO free radicals and ha ve substantially same spectroscopy as that of 1. The free radical scavenging tests in vitro, euglobulin lys is tests in vitro and the thrombolysis tests in vivo indicated that couplling 1 and P6A or its analogues re sulted in the combination of free radical scavenging and thrombolysis actions. F or instance as H₂ O₂ scavenger the EC₅₀ of 2a-c and 1 is 28.1, 25.4, 24.1 and 30.2 μmol/L, respectively. As·OH scavenger the EC₅₀ of 2a-c and 1 is 98.1, 95.4, 94.2 and 100.0 μmol/L. As NO scavenger the EC₅₀ of 2a-c and 1 is 89.1, 9 2.3, 91.8 and 91.2 μmol/L. Comparing to 1 the free radical scavenging activities are increased. After adm inistration of 10.0 μmol/L of 2a-c,1, UK and NS the reduced thrombus mass is (19.91± 3.59)mg,(19.70± 3.76)mg,(28.85± 3.80)mg,(15.89 ± 2.53)mg,(25.40± 2.50)mg and (15.11± 3.70)mg, respectively. After administration of 10.0 μmo l/L of A RPAK, GRPAK and QRPAK the reduced thrombus mass is (18.54± 3.28)mg,(21.17± 3.06)mg and (25.82± 2.15)mg respectively. All of the mentione d data indicated that the nitronyl nitroxide modified peptide 6A and analogues po ses both of free radicals scavenging activity and thrombolysis activity.

Evaluation of Enzyme Induction Effect of Schisandra Chinensis and Glycyrrhiza Uralensis on Pharmacokinetics of Lidocaine in Rats

Tang Jingcheng;Zhang Jinnan;Li Yawei

2005, 26(1):  43-43. 

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Drug-drug interaction potentials of two herbal medicines, namely Schisandra chi nensis and Glycyrrhiza uralensis, were investigated in rats via in-vitro and in-vivo pharmacokinetic studies.Male SD rats received Schisandra or Glycyrrhiza decoction once daily for 6 days at doses equivalent to 1g or 3 g/kg. Rats receiving distil wat er and Phenobarbital (0.12 g/kg) were used as non-treatment and positive contro ls, respectively. The liver was collected for the preparation of microsomes, and P₄₅₀ levels were measured for different treatment groups. In a separate s tudy, lidocaine was employed as probe compound, and its metabolic rate in the liver mi crosomes prepared from the rats pretreated by Schisandra or Glycyrrhiza or Pheno barbital for 6 days was examined. In the in-vivo pharmacokinetic study, rats we re pretreated with Schisandra or Glycyrrhiza for 6 days. Lidocaine was administ ered on day 7 intravenously at 10 mg/kg dose. Pharmacokinetic parameters of lido caine in plasma and urine were estimated.P₄₅₀ levels in the rats pretreated by Schisandra or Glycyrrhiza were signi ficant higher than that in the non-treatment control. The increase in P₄₅₀ was dose-dependent and time-dependent. On day 6, Schisandra, Glycyrrhiza and Phen obarbital increased P₄₅₀ levels by 58%, 91% and 270% compared to the non-treatm ent control (0.695 μmol/g protein). Metabolic rate of lidocaine in the live r mi crosomes was significantly higher in rats that received Schisandra, Glycyrrhiza or Phenobarbital pretreatment when compared to the non-treatment control. Pharm acokinetic profile of lidocaine was significantly modified in the rats with the herbal pretreatment. Elimination half-lives were shorten by 28% and 39%, and to tal clearances were increased by 76% and 59% in the Schisandra and Glycyrrhiza g roups, respectively.In conclusion, Schisandra and Glycyrrhiza showed induction effect on P₄₅₀ isozymes. Efficacy and safety profiles of a drug may be affected when the herbal products or herbal prescriptions containing these two plant medicines were conc omitantly used.

Determination of Moxonidine in Human Plasma by LC-MS and Study of Bioequivalence of Moxonidine Preparation

Wei Xin

2005, 26(1):  44-44. 

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Moxonidine hydrochloride is a new centrally-acting antihypertension agent that reduces blood pressure by stimulating the central α 2-adrenoceptor. The purpo se of the present study was to develop a method for loperamide hydrochloride bio equivalence testing. For this purpose, a simple rapid and selective LC-MS metho d utilizing a single quadrupole mass spectrometer was developed and validated fo r the determination of moxonidine hydrochloride in human plasma, and we followed this with a bioavailability study.Clonidine hydrochloride was used as the internal standard. After being made alka line, plasma was extracted by ethyl acetate and separated by HPLC on a reversed-phase C₁₈ column (5 μm, 4.6 mm×250 mm). HPLC-ESI-MS was performed in the selected ion monitoring (SIM) mode using target ions at m/z 242.2 for mo xonidine and m/z 230.1 for the internal standard. The retention times of moxonid ine hydrochloride and IS were 3.0 and 3.1 min, respectively. Endogenous substanc es didn't interfere the determination of moxonidine. Calibration curve was linea r over the range of 0.019 76～9.88 μg·L^-1. The limit of quantification for moxonidine hydrochloride in plasma was 0.019 76 μg·L^-1. The describ ed assay method showed acceptable precision, accuracy, linearity, stability, and specificity.A randomized crossover design was performed in 20 healthy volunteers. In the two study periods,a single 0.2 mg dose of each formulation was administered to eac h volunteer. The main pharmacokinetics parameter t_1/2, t_max and c_max were (2.86±0.33)h,(0.55±0.17)h and (1.61±0.29)μg·L^-1for the reference tablet;(2.79±0.24)h,(0.65±0.21)h and (1.62 ±0.34)μg·L^-1 for the test capsule,respectively. The relative bioavailability of the test capsule was (100.1±9.9)%. The assay was proved to be sensitive,accurate and convenient. The two formu lations were bioequivalent.

Study on the Pharmacokinetics of Pesudoephedrine/Loratadine Extended-release Tablet in Healthy Volunteers

Wei Xin

2005, 26(1):  45-45. 

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The extended-release pesudoephedrine/loratadine twice-daily combination tablet formulation has been shown to be safe and effective for the relief of symptoms associated with allergic rhinitis. Each tablet consists of laratadine 5 mg in an immediate-release coating and pseudoephedrine sulfate 120 mg, of which 60 mg i s in a barrier-protected core. We have established an LC-ESI-MS method for si multaneous determination of pesudoephedrine/loratadine and its metabolite(DCL) i n human plasma, which was proved to be sensitive,accurate and convenient. By th is means, we have investigated the characteristic of its pharmacokinetics in hum an. In the two study periods, subjects received a single dose and multiple doses (days 1 to 6) of twice-daily formulation. After a single dose, the main pharm acokinetics parameters of t_1/2, t_max, c_max, and AUC_0-36 were (6.9±1.4)h,(4.3±3.2)h,(311.3±50.2)μg·L^-1 a nd(4 312±678)μg·(h·L)^-1 for pseudoephedrine;(6.8±1.7)h,(1.4 ±0.4)h,(2.46±1.88)μg·L^-1 and(8.93±6.19)μg·(h·L)^-1 for lor a tadine;(15.6±4.7)h,(2.0±1.0)h,(2.76±1.80)μg·L^-1 and(20.63±1 1.33)μg·(h·L)^-1 for DCL, respectively. After multiple doses (days 1 to 6), the main pharmacokinetics parameters of Cav, DF, and AUCss were (337.4±49.4)μg·L^-1, (0.72±0.28)% and(4 049±594)μg·(h·L)^-1 for ps eudoep hedrine; (0.86±0.74)μg·L^-1, (3.05±1.37)% and (10.38±8.86)μg·(h·L)^-1 for loratadine; (1.31±0.76)μg·L^-1, (2.18±0.82)% and (15.69±9.14)μg·(h·L)^-1 for DCL, respectively.In conclusion, Loratadine is extensively metabolized in the liver to an active m etabolite(DCL), so first pass has resulted in obvious difference within the vo lunteers. In contrast with the common formulation, this twice-daily combination tablet formulation has showed the character of extended-release. After a singe l dose, t_1/2 and t_max of pesudoephedrine have been increased, and the same time, c_max has been reduced. After multiple doses, DF of pesudoephedrine was little. The time-concentration curve of pesudoephedrine sulfate has two peaks, which wa s the proof of immediate-extended release coating.

Effects of PEG Chain Lengths and Charges of Surfactants on the Physical Stability of a Marine Oil-in-Sater Emulsion

Cui Guohui;Wang L;Davis P J;Kara M;Liu H

2005, 26(1):  46-46. 

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Oil-in-water emulsion formulations often contain vegetable oil such as soybean oil as the core component. In the current study, oil derived from harp seals, rich in ω-3 long chain fatty acids, was used. The effect of different polyet hleneglycols (PEGs) coated on hydrogenated castor oils as emulsifying agents on the physical stability of seal oil-in-water emulsions was studied. It was fou nd that 2.5% PEG-40 coated hydrogenated castor oil (Croda-RX40, HLB 13) formed the most stable 10% of seal with diameter of 240-270 nm. The effe ct of surface charge on the physical stability of seal oil emulsions was also st udied by adding different amounts of either negatively charged surfactant (Croda,sinic LS-30) or positively charged surfactant (Incroqal Behenyl TMS). The neg atively charged Croda,sinic LS-30 had very little effects on the particle sizes. For the positively charged surfactant such as Incroquat Behenyl TMS, there w ere big fluctuations of particle sizes, especially in the concentrations of 0.25 % and 0.5%. pH values of 10% of seal oil emulsions were found to decrease over the time because of the hydrolysis of triacylglycerides into free fatty acids. The current studies demonstrated that the stable emulsion systems could be form ed when the absolute Zeta-potential value exceeds ^*20 mV^*, regardless of the po sitive or negative charges on the surface of emulsions.

Preparation of CEC Stationary Phase for High-Speed Analys is

Yang Changhua;Xu Bingjiu

2005, 26(1):  47-47. 

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Bonded stationary phase of sub-micron diameter for the preparation of columns f or capillary electrochromat-ographic analysis was prepared. The procedure was as follows: From a raw material of the mixture of tetraethoxy-silane and triet hoxy vinylsilane, an inorgano-organo hybrid siliceous particles with bonded vin yl groups were prepared using the Sol-gel technique. On the basis of the prepa red particles, copolymer of methoxy styrene-styrene-divinylbenzene was encapsu lated onto its surface to prepare a new kind of stationary phase.The new stationary phase was packed into capillary columns (i.d. 0.32 mm) and their electrochromatographic characteristics tested. It was found that much higher analytical speed could be obtained on this new phase.From the electrochromatogram obtained on a previously synthesized stationary pha se which used the same matrix and which was encapsulated with polystyrene a poly mer containing no methoxy groups, it can be seen that although the applied volta ge was 15 kV, the non-retaining solute, thiourea, eluted the column in as much as 3.9 min, benzene, toluene and naphthalene eluted the column in 4.9, 5.1 and 6.32 min, respectively; whereas on the column of the same length packed with met hoxystyrene polymer encapsulated phase of similar length, thiourea eluted the co lumn in only 0.53 min, and benzene, toluene and naphthalene eluted the column in 0.53, 0.62, 0.69 and 0.79 min, respectively. Thus this kind of high-speed elec trochr omatographic stationary phase can offer analytical speed several times higher th an “normal” phases. For the abovementioned solutes, the ratio between their re tention times on the two kinds of stationary phases were 7.3,7.9,7.4 and 8.0, respectively.The reason of the aforementioned high analytical speed might be elucidated as fo llows: the methoxy groups on the stationary phase surface might result in some p henolic hydroxyl groups (upon preparation of the columns we rinsed the columns w ith acidic solution, this probably hydrolyzed the methoxy groups, producing phen olic hydroxyl groups). These hydroxyl groups resulted in higher electroosmotic f low, and the latter in turn greatly boosted the analytical speed.

PD98059 on Heart Function Endured 11,12-EET and Ischemia Preconditioning

Wang Hongxia;Zeng Xiangjun;Yan Li;Lu Lingqiao;Zhang Like

2005, 26(1):  48-50. 

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The aim was to investigate the effect of PD98059 on heart function endured 11, 12-EET a nd ischemia preconditioning and know about the effect of the expression of phosp horylated ERK1/ERK2 on the cardiac protection. Adopting ligating 60 min a nd releasing 30 min to make a ischemic/reperfusion model; ligating 5 min and rel ea sing 5 min (two times) to replicate ischemic preconditioning model. Observing th e changing of heart function during reperfusion process and detecting the expressi on of ERK1/ERK2 through western blot method. There was significant di fferen ce contrasting the heart function I/R group with SI+I/R and EET+I/R group, and t he heart function was significantly decreased after PD98059 infusion. The phosph orylated expression of ERK of I/R group was significantly lower than SI+I/R and E ET+I/R group, and the phosphorylated expression of ERK was significantly decreas ed after PD98059 infusion. It suggests that 6.24×10^-8 mol/L 11,12-EET h as the effect of protecting myocardium function that is inducted by increasing the expression of phosphorylated ERK1/ERK2.

17β-estradiol and Phytoestrogen α-zearalanolon Uterus Enlarging in Ovariectomized Rats

Wang Wen;Yang Hui;Wang Hongxia;Zhang Like

2005, 26(1):  51-54. 

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The aim of this study was to investigate and compare the effects of 17β-estrad iol and phytoestrogen α-zearalanol(ZAL) on uterus enlarging in ovariectomized(OVX) rats. OVX rats were injected intramuscularly with 17β-estradiol or ZAL (1 mg/kg) for five weeks. The concentrations of plasma estradiol were measured by radioimmunoassay. Separate the uterus from rats and calculate the ratio of ut eri weight(g)/body weight(kg) then make pathology slice of uterus tissue. It was found that plasma estradiol levels of OVX+17β-estradiol rats were signifi cantly higher than th at of OVX rats, while estradiol levels of OVX+ZAL were significantly lower than that of OVX+17β-estradiol rats. ZAL had slighter effect on uterus enlarging in ovariectomized rats compared with 17β-estradiol. These results suggest that Z AL has less stimulation on uterus than 17β-estradiol, which maybe work as one of selectively estrogen receptor modulator(SERM).

Expansion and Differentiation of Human Umbilical Cord Blood Cells Into Neuronlike Cells

Ji Fengqing;Sun Haimei;Zeng Xiaobei;Li Baohong;Zhang Hua;Wang Xiuqin;Yang Hui;Lu Lingling;Zhao Chunli

2005, 26(1):  55-58. 

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The aim was to explore the isolation, purification and differentiation of umbil ical cord blood cells into neuronlick cells in vitro. Human cord blood samples were obtained, cultured and induced with fectors. Identification was performed with immunochemistry method. Umbilical cord blood could proliferate an d generate clones when cultured in vitro. These cell grew rapidly and different iated into neuronlike cells and astrocytelike cells. The cell clones proliferate d from stem cell could express nestin antigen and the differentiated cells expre ssing GFAP or NSE antigen respectively. In this study, bFGF and EGF in fluencing the induction and differentiation of Umbilical cord blood were observed. It suggests that umbilical cord blood cells have selfrenewal and differentiat ion abilities. They might differentiate into neuronlike and astrocytelike cells which express GFAP or NSE. The umbilical cord blood can be considered the ideal seed cells of the neural stem cells.

Hyperbaric Oxygen on Expression of Caspase-3 in Mouse Hippocampus after Transient Forebrain Ischemia

Liu Tianhui;Chen Rui

2005, 26(1):  59-62. 

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This study was to observe the effect of hyperbaric oxygen (HBO) on the expressio ns of caspase-3 in hippocampus following transient forebrain ischemia, and to find out the possible mechanism of HBO treatment. C57BL/6N mice were divided into three groups: sham-operated group (control), ischemia/reperfusion(I/R) group and HBO treatmen t after I/R group. Transient forebrain ischemia was induced by bilateral common carotid artery occlusion for 20 min. Hippocampus was obtained at reperfusion ti me poin ts of 6 h, 12 h, 24 h and 48 h respectively after 20 min of ischemia. RT-PCR wa s used to detect the expression of caspase-3 mRNA, and Western Blotting was use d to detect the level of caspase-3 protein. Experimental data showed that caspase-3 mRNA and procaspase-3 level increased in hippocampus in I/R groups and HBO groups. The difference was significant(P< 0.05) when compared with express ion levels in sham-operated mice. There was no significant alteration in expres s ion levels between every I/R group and HBO treatment group of corresponding time point(P> 0.05). These data indicate that ischemia/reperfusion which induces caspase-3 mRNA expression and increases transcription of caspase-3 is the mean reason fo r procaspase-3 increase. Caspase-3-dependent apoptosis is involved in ischemia /re perfusion injury. The HBO treatment project has no significant effect on caspase-3 mRNA and procaspase-3.

Differential Expression of Signal Transduction Related Genes on Human Cerebral Aneurysms

Yang Lei;Zhao Jizong;Wang Shuo;Zhang Dong;Zhao Yuanli;Dong Jianling

2005, 26(1):  63-66. 

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The aim was to study the expression of signal transduction related genes on huma n cerebral aneurysm s with microarray gene chip. 8 464 genes of the PCR products were spotted onto a glass plates in array. DNAs were fixed onto the glass plate. The total RNAs wer e isolated from the tissue, and were purified to mRNAs by Oligotex. Both mRNAs f rom the 4 human cerebral aneurysms and normal human Willis circle arteries were reversely transcribed to cDNAs with hybridization probes using the incorporation of Cy3-dCTP and Cy5-dCTP. The mixed probes were hybridized to the cDNA micr oarray. The cDNA microarray was scanned for the fluorescent signals and showed d ifferences between aneurysm and normal control. Among the 8 464 target genes, 15 signal transduction related genes showed significant different expression betw een aneurysms and normal control with 13 genes upregulated and 2 genes downregul ated. The differentially expressed genes and related pathology can play a key role in the pathogenesis of cerebral aneurysms.

Clinical Analysis and Surgical Therapy of Moyamoya Disease in Children

Jin Qiang;Li Jian;Zhao Jizong

2005, 26(1):  67-69. 

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The research was based on 68 cases of moyamoya disease in ch ildren between 1986 and 2002 in Tiantan Hospital and they received operations th r ough four kinds of surgical methods at random. Comparison and analysis of the therapeutic effects of four operative methods of cerebral revascularization were m ade through statistics methods. The result showed that all of the surgical me thods in the research were effective. However, there was no significant differen ce between these surgical methods as far as therapeutic effects were concerned. Fu rthermore, it suggests that it is necessary to select convenient, safe dimin-v ulnerarious surgical methods for patients. The researcher must try their utmost to explore the etiology of MMD to find reliable and effective therapies.

Anatomic Research of Retrosigmoid Transsuprameatal Approach

Gong Jian;Yu Chunjiang;Guan Shusen;Wang Fengmei;Chen Fei

2005, 26(1):  70-73. 

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It was an anatomic research on the Retrosigmoid Transsup rameatal Approach (RTA) to remove TypeⅡpetroclival meningiomas. It researched o n 10 adult cadaver heads fixed in 10% formalin and 10 dry human skulls. 10 cadaver heads were examined by bone-window CT scanning before and after operation. Important anatomic structure and position relationship were measured and photographed. For the RTA, the important structures included petrous vei n, inner audition artery and suprameatus. The important data included the scope of the bone window. It suggests that it is the petrous apex maxim um drilling scope, through which the middle fossa part of the tumor could be rem oved. It's characterized by simplicity, security and minimal invasion.

Supraorbital Keyhole Approach to Tumors of Anterior Fossa and Sellar Region

Qi Wei;Zhang Maozhi;Zhang Wei;Wang Lei;Wang Rong

2005, 26(1):  74-76. 

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The purpose of this study was to evaluate the results of the supraorbi tal keyhole approach performed on tumors of the anterior fossa and sellar region. Altogether 39 patients with tumors of the anterior fossa and sellar region wer e operated upon by using this approach traditional subfrontal approach were oper ated upon by and 36 patients. The surgical resu lts were analyzed prospectively and compared. It showed no difference in th e tumor resection degree, main complicatio ns and tumor recurrence between the two different approaches. But patients who w ere operated on and received the supraorbital keyhole approach had less operativ e trauma, achieving good out-looking and shorter hospitalization. It suggests t hat the supraorbital keyhole approach with a eyebrow skin incision is a safe and convenient minimal-invasive approach for experienced micro-neurosurgeons in t he treatment of lesions of the anterior fossa and sellar region.

Molecular Biology Mechanism for Secondary Injury to Perihematoma in ICH Rats

Zhao Xingquan;Wang Yongjun;Wang Chunxue;Zhou Jian;Wang Yuanshen;Ji Man

2005, 26(1):  77-80. 

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The aim was to study possible molecular biology mechanism of secondary lesion to perihematom a tissue in intracerebral haemorrhage (ICH) rats by testing HSP70, NF-κB, Bax, Bcl-2 of surrounding tissue of hematoma through immunohistochemistry met hod. Sp rague-Dawley male rats were subjected to ICH models. They were randomly divide d into test groups and control groups. Test groups were divided into 7 subgroups at 1 h, 3 h, 12 h, 24 h, 48 h, and 72 h after ICH, control groups were divided into 3 subgroups at 3 h, 24 h, 72 h after normal saline injection. HSP70, NF-κB, Bcl-2, Bax were tested by immunohistochemistry staining at perihematoma area. Positive cells were picked up by HP1000 high-definition colorful pathology im aging analysis system and compared with the control subgroups. HSP70 and NF-κB expressed the most at the hematoma side at 72 h after surgery (P<0.01); The y demonstrated significant difference among subgroups compared with control subgro ups. Bcl-2 expressed the highest at 12 h after surgery (P<0.01) and Bax at 24 h after injection (P<0.01); Bcl-2 and Bax showed significant difference among subgroups compared with control groups (P<0.01). The result suggests t hat dynamic alternation of HSP70, NF-κB, Bcl-2 and Bax participates and plays an important role in the pathologic process of secondary injury to perihematoma tissue.

Clinical Significance and Variation of CD62P and Pac-1 in Patients with Acute Coronary Syndrome

Wan Yungao;Hua Qi;Wan Suigui;Xu Juan

2005, 26(1):  81-83. 

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The aim was to assess clinical significance and variation of CD62P and Pac-1 i n patients wi th acute coronary syndrome (ACS). The alphagranulemembrane protein (CD62P) and P ac-1 from whole-blood samples in 66 patients with ACS on attack or on stable period were measured by FCM and monoc lonal antibody. The 66 patients with ACS including 44 with unstable angina pecto ris (UAP) and 22 with acute myocardial infarction (AMI). Meanwhile age-sex matc hed 22 healthy persons were selected as controls. There were significantly highe r platelet CD62P and Pac-1 expression in patients with ACS on attack than those in controls (P<0.05), but platelet CD62P and Pac-1 expression were signif icantly lower after one month therapy in patients with ACS, but still significan tly higher than controls (P<0.05). It suggests that platelet activation is high in patients with ACS, platelet CD62P and Pac-1 expression can be the effec tive index of monitoring coronary heart diseases.

Diagnosis and Treatment of Noncardiac Complication Following Angiograph and Angioplasty

Guo Jincheng;Hua Qi;Liu Lisong;Yao Liyun;Li Kang;Zhang Xuekun;Wan Yungao;Zhang Lixin;Zhang Haibin

2005, 26(1):  84-86. 

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The ai m was to evaluate the diagnosis and treatment of non-cardiac complications foll owing coronary interventional procedure. Non-cardiac complications of 4 435 pat ie nts underwent cardiac intervention were analysed. It find that the total noncard iac complications rate was 1.3%, including severe external hemo rrhage 0.09%, retroperitoneal hematoma 0.02%, femoral pseudoaneurysm 0.9%, pulmo nary thromboembolism 0.02%, blue toe syndrome 0.05%, femoral dissection 0.07 %, femoral penetration 0.02 %, severe contrast allergic shock 0.05%, stroke 0.05%, femoral thrombus 0.02 %. D eath occurred in 1 patients due to pulmonary thromboembolism after one day of an giograpm, and no sequela occurred in other patients. It suggests that Non-cardi ac c omplications following coronary interventional procedure through femoral artery are common and have good results after immediate diagnosis and treatment.

Lipid-lowering Treatment on Plasma Insulin Level

Li Hongbing;Wu Baoyu;Liu Wei;Xie Rongrong

2005, 26(1):  87-89. 

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The aim was to approach the effect of lipid-lowering treatment on insuli n resistance in patients with type 2 diabetes mellitus. Eighty-four type 2 diab etic patients associated with dyslipidemia were treated by antihyperlipoidemics. 49 patients were treated with 20 mg simvastatin and 35 patients were treated wit h 0.2 g fenofibrate per day. The antihyperglycemic and antihypertensive ther apies were maintained. Before and after the treatment, all of patients w ere examined body mass index(BMI), waist-line/hip-line rate(WHR), blood pressu re, glycosylated hemoglobic (HbA1c), plasma fasting insulin (FINS), total choles terol(TC), total triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol(LDL-C). After 12 weeks of follow up,the TC, TG, and LDL-C levels decreased obviously(P<0.01). HDL-C level in creased obviously in the lipanthyl group (P=0.037). The plasma fasting insul in level decreased from (10.93±5.03) to (9.28±4.26) IU·L^-1 (P<0.01). There were no difference in the fasting plasma insulin level when the simvast atin treated group were compared with the fenofibrate treated group. It suggests that the resistance of insulin improves lipid-lowering treatment in type 2 dia betic patients.

Retrospective Analysis of 40 Cases of Placenta Increta

Zhou Li;Wu Lianfang

2005, 26(1):  90-92. 

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The aim was to study the factors related with placenta increta and treatment by retrospectively. The etiology of the placenta incr eta and t he treatments were studied by retrospectively analyzing 40 cases. The incidence of placenta increta in our hospital approxi mated to 1:1 011 and the related risk factors include placenta previa, previou s cesarean delivery, and multiple induced abortion. There were about 75% cases w ith above 2 times of induced abortion, 27.5% cases with cesarean and 55% cases with placenta previa. The incidence of h emorrhage (>500 mL) was up to 62.5% when the patients had the completely placent a pr evia and the diameter of the implanted placenta >5 cm. There were about 86% case s of placen ta previa with serious hemorrhage and the amount of bleeding of above 2 000 mL in the 5 cases in which the placenta was implanted the previous cesarean sectio n scar.The incidence of placenta increta was increased with placenta previa, previous cesarean delivery, and multiple induced abortions. Placenta increta ind uces serious puerperal hemorrhage, especially, the placenta implanted in the pre v ious cesarean section scar. The conservative therapies are very important as we ll as hysterectomy.